As this RFA emphasizes, the prevalence rates of overweight/obesity, type 2 diabetes (T2DM), and the Metabolic Syndrome (MS: a constellation of metabolic abnormalities such as obesity and impaired glucose tolerance) have been increasing at epidemic proportions, particularly in minority groups such as Mexican Americans. However, the mechanisms that underlie the MS in children are unclear, and it is also not clear whether or not the precursors of the MS in children are the same as those in adults. If so, attempts to establish the precursors of the MS in children as well as to develop biomarkers and/or genetic markers that could help identify children at risk for the MS later in life, are of the utmost importance in developing effective strategies to prevent or treat children that are at high risk for the MS. The purpose of this proposal is to establish the precursors of the MS in Mexican American Children. Given that family history of T2DM is an important factor associated with the MS risk, plans to establish the precursors of the MS in children could be greatly advanced by examining the children of previously established adult family-based cohorts such as ours that are enriched with prediabetic and diabetic individuals. Added advantages of our design include the readily available MS-related data in adults, and already localized genomic regions that harbor the MS genes. In this context, we plan to examine 750 children (aged 6-17 years) of the adults representing distinct families in our ongoing San Antonio Family Birth Weight Study, who are the original participants of the three well-established Mexican American family studies, to establish the precursors of MS. The major goals of this project are: 1) to examine 750 children (aged 6-17) years of the adults representing various families in our ongoing San Antonio Birth Weight Study in order to measure various MS-related phenotypes (e.g., obesity, impaired glucose tolerance, dyslipidemia, and hypertension) and environmental factors such as physical activity and fitness; 2) to compare the MS risk profiles of the children to those already established in the adults of our family studies to verify whether or not the etiological mechanisms underlying the MS are different between children and adults using different analytical tools including the NCEP/ATPIII definition of the MS, factor analysis, and bivariate genetic analysis; and 3) to examine the association between MS phenotypes in children and 10 genetic markers (single nucleotide polymorphisms, SNPs) selected from each of 25 key positional and other candidate genes that we have identified, primarily from our ongoing linkage/association analyses, as potentially influencing MS phenotypes in adults. In sum, this study provides an unusual opportunity to contribute to a better understanding of the MS in Mexican Americans, both children and adults.